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Case 1 36 year old woman presented with atypical facial pain admitted to Teaching Service. Physical examination was normal. Past history: depression, anxiety and Mollaret’s meningitis. Meds: Trazodone, venlafaxine, chlorazepate; valacyclovir Started on gabapentin (Neurontin) with no pain relief. Switched to carbamazepine (Tegretol) with no pain relief. A few weeks later, she developed a severe generalized pruritic maculopapular rash, “granulomatous” hepatitis, and eosinophilia (35%), treated with prednisone and hydroxyzine. She then developed CNS vasculitis with multiple strokes (carbamazepine hypersensitivity syndrome [CHS] with CNS vasculitis).

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Case 2 53 year old woman referred for chronic upper and lower abdominal pain and constipation. Past history of anxiety, depression, stress, perineal pain, fibro- myalgia, nonulcer dyspepsia, and hysterectomy/oophorectomy. Recent flare of pain led to laparoscopic appendectomy, with no pain relief (and no abnormality of the appendix on path exam). Common bile duct was slightly dilated (10 mm) on ultrasound [history of cholecystectomy 20 years ago for upper abdominal pain]. GI was consulted and an ERCP was attempted, complicated by acute pancreatitis requiring hospitalization. Physical exam and lab studies at this time were normal. Abdominal pain and constipation improved with the 5-HT 4 agonist tegaserod (Zelnorm). Her dyspepsia did not improve and was treated with a PPI with minimal relief. She is being seen by at least 3 gastroenterologists currently.

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Case 3 22 year old woman (daughter of a physician) referred because of flushing, abdominal cramps, and loose stools after eating. She is unable to attend school or work due to her GI symptoms. –Negative or normal: colonoscopy X2; stool fat; urine 5-HIAA, sprue panel, EGD, CT, octreoscan, EUS, etc. Past medical history of obesity, “PCOS” [with normal ovarian sonogram], asthma, multiple food sensitivities/allergies, chronic headaches, myalgia and arthralgia compatible with FM, multiple knee surgeries, possible Sjögren’s syndrome. Taking 23 medications from numerous specialists such as an allergist/pulmonologist and endocrinologist, including prednisone and octreotide. Exam (with parents present): morbidly obese and Cushingoid with buffalo hump and hundreds of red and purple striae, but otherwise well-appearing. Exam was otherwise normal and laboratory studies were all normal.

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Working definitions Symptom: a patient’s subjective experience of a change in his/her body Disease: an objective, observable abnormality in the body When we can find no objective change to explain the patient’s subjective experience, we term the symptoms “medically unexplained” or “functional”.

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A case for Lumping Argument 1 There is a great deal of overlap in case definitions of specific syndromes. Of 12 “specific” syndromes analyzed by Wessely et al, the definition of the syndrome included: –Bloating/feeling of abdominal distention in 8 –Headache in 8 –Fatigue in 6 –Abdominal pain features in 6

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Rome III. Psychosocial aspects of the functional GI disorders. Levy et al. Gastroenterology 130: 1447-58, 2006. The committee reached consensus in finding considerable evidence supporting the association between psychological distress, childhood trauma and recent environmental stress, and several of the FGIDs but noted that this association is not specific to FGIDs. … there is now increasing evidence that a number of psychological treatments and antidepressants are helpful in reducing symptoms and other consequences of the FGIDs in children and adults.

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Multiple Chemical Sensitivity (MCS) Syndrome Several theories have been advanced to explain the cause of MCS, including allergy, toxic effects and neurobiologic sensitization. There is insufficient scientific evidence to confirm a relationship between any of these possible causes and symptoms. Patients with MCS have high rates of depression, anxiety and somatoform disorders, but it is unclear if a causal relationship or merely an association exists between MCS and psychiatric problems. Physicians should compassionately evaluate and care for patients who have this distressing condition, while avoiding the use of unproven, expensive or potentially harmful tests and treatments. The first goal of management is to establish an effective physician- patient relationship. The patient's efforts to return to work and to a normal social life should be encouraged and supported. Magill and Suruda. Amer Fam Physician, September, 1998